Genetic risk of ADHD probed as biomarker of Alzheimer’s disease

the study covered in this summary was posted on as a preprint and has not yet been peer reviewed.

Key points to remember

  • Elderly patients with a high polygenic risk score for attention deficit hyperactivity disorder, but without a clinical diagnosis of ADHD, are at high risk for progressive longitudinal cognitive deterioration.

  • Cognitive decline was most common in people with PET-confirmed amyloid-β (Aβ) pathology, suggesting that people with genetic responsibility for ADHD and those who are Aβ-positive have cognitive susceptibility.

  • Longitudinal increases in cerebrospinal fluid (CSF) p-tau181 and cerebral atrophy in the frontal and parietal regions was associated in Aβ-positive individuals with elevated ADHD-PRS scores, suggesting an elevated susceptibility to tau pathology in ADHD patients.

why it matters

  • Although cognitive deficits in various neurocognitive domains have been widely described in ADHD, no studies have yet established a link between ADHD and a decline in cognitive performance in adults or with the progression of dementia from ADHD. Alzheimer’s.

  • This study used a well-validated ADHD polygenic risk score (ADHD-PRS) to support epidemiological associations between ADHD and cognitive decline and the development of Alzheimer’s disease in adults without cognitive impairment.

  • The results of the study indicate that ADHD-PRS may shed light on the risk of developing cognitive decline in the cognitively intact older population in the absence of Alzheimer’s disease biomarkers.

study design

  • Researchers used data from the Alzheimer’s Disease Neuroimaging Initiative to develop clinical, imaging, genetic and biochemical markers for the early detection and monitoring of Alzheimer’s disease.

  • They used whole-genome information to calculate a weighted ADHD-PRS in 212 people without cognitive impairment aged 55 to 90 who did not have a clinical diagnosis of ADHD.

  • Baseline Aβ PET and baseline medical data were available for all study participants, and all had undergone at least two clinical neuropsychological assessments.

  • Patients with major depression or bipolar disorder in the year prior to enrollment were excluded from the study, as were people with a history of schizophrenia and people with a geriatric depression score greater than 6 .

Principle results

  • At baseline, all 212 participants had a clinical dementia score of 0, 196 had longitudinal CSF p-tau181 data available and 193 had MRI data available. The average age of study participants was 73.1 years and 54.7% were female.

  • Elevated ADHD-PRS was more likely to be associated with cognitive decline over the 6-year study period, and was also associated with elevated CSF p-tau.181 and frontoparietal atrophy in Aβ-positive individuals.

  • The combined effect of elevated ADHD-PRS and brain Aβ deposition on cognitive impairment was greater than either factor alone.


  • No details on the clinical assessment of the diagnosis of ADHD in study participants were reported.

  • Patients with neuropsychiatric disorders – such as depression, bipolar disorder and schizophrenia – were excluded from the study, which limits the external validity of the results.

  • In ADHD populations treated in clinical centers, psychiatric comorbidities are common, but in this study cohort there would have been fewer comorbidities, affecting the generalizability of the results.

  • Most of the study participants were white.


  • The study received no commercial funding.

  • Among the authors, Luis Augusto Rohde, MD, PhD, has received research grants and has consulted for Ache, Bial, Medice, Norvartis, Pfizer and Shire; has received copyright royalties from ArtMed; and acted as a consultant for Knight Therapeutics.

This is a summary of a preprint research study, Genetic Risk for Attention-Deficit/Hyperactivity Disorder Predicts Cognitive Decline and Development of Alzheimer’s Disease Pathophysiology in Cognitively Unimpaired Older Adults, written by researchers from the Department of Psychiatry at the University of Pittsburgh , the Department of Neuroscience at King’s College London, and the Alzheimer’s Disease Neuroimaging Initiative, published on medRxiv and made available to you by Medscape. The study has not yet been peer reviewed. The full text of the study is available at

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